Faculty Bibliography

OBJECT: The object of this study was to evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVMs). METHODS: Between 1987 and 2006, Gamma Knife surgery was performed in 996 patients with AVMs. During this period, repeat SRS was performed in 105 patients who had incompletely obliterated AVMs at a median of 40.9 months after initial SRS (range 27.5-139 months). The median AVM target volume was 6.4 cm(3) (range 0.2-26.3 cm(3)) at initial SRS but was reduced to 2.3 cm(3) (range 0.1-18.2 cm(3)) at the time of the second procedure. The median margin dose at both initial SRS and repeat SRS was 18 Gy. RESULTS: The actuarial rate of total obliteration by angiography or MR imaging after repeat SRS was 35%, 68%, 77%, and 80% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographic or MR imaging obliteration after repeat SRS was 39 months. Factors associated with a higher rate of AVM obliteration were smaller residual AVM target volume (p = 0.038) and a volume reduction of 50% or more after the initial procedure (p = 0.014). Seven patients (7%) had a hemorrhage in the interval between initial SRS and repeat SRS. Seventeen patients (16%) had hemorrhage after repeat SRS and 6 patients died. The cumulative actuarial rates of new AVM hemorrhage after repeat SRS were 1.9%, 8.1%, 10.1%, 10.1%, and 22.4% at 1, 2, 3, 5, and 10 years, respectively, which translate to annual hemorrhage rates of 4.05% and 1.79% of patients developing new post-repeat-SRS hemorrhages per year for Years 0-2 and 2-10 following repeat SRS. Factors associated with a higher risk of hemorrhage after repeat SRS were a greater number of prior hemorrhages (p = 0.008), larger AVM target volume at initial SRS (p = 0.010), larger target volume at repeat SRS (p = 0.002), initial AVM volume reduction less than 50% (p = 0.019), and a higher Pollock-Flickinger score (p = 0.010). Symptomatic adverse radiation effects developed in 5 patients (4.8%) after initial SRS and in 10 patients (9.5%) after repeat SRS. Prior embolization (p = 0.022) and a higher Spetzler-Martin grade (p = 0.004) were significantly associated with higher rates of adverse radiation effects after repeat SRS. Delayed cyst formation occurred in 5 patients (4.8%) at a median of 108 months after repeat SRS (range 47-184 months). CONCLUSIONS: Repeat SRS for incompletely obliterated AVMs increases the eventual obliteration rate. Hemorrhage after obliteration did not occur in this series. The best results for patients with incompletely obliterated AVMs were seen in patients with a smaller residual nidus volume and no prior hemorrhages.

We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46-72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5-34.5 months). The median tumor volume was 13.6 cm(3) (range 1.2-45.1 cm(3)) and the median margin dose of GKSR was 16 Gy (range 13-18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6-28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5-23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1-25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy.

OBJECT: Vertebrobasilar ectasia (VBE) is an unusual cause of trigeminal neuralgia (TN). The surgical options for patients with medically refractory pain include percutaneous or microsurgical rhizotomy and microvascular decompression (MVD). All such procedures can be technically challenging. This report evaluates the response to a minimally invasive procedure, Gamma Knife surgery (GKS), in patients with TN associated with severe vascular compression caused by VBE. METHODS: Twenty patients underwent GKS for medically refractory TN associated with VBE. The median patient age was 74 years (range 48-95 years). Prior surgical procedures had failed in 11 patients (55%). In 9 patients (45%), GKS was the first procedure they had undergone. The median target dose for GKS was 80 Gy (range 75-85 Gy). The median follow-up was 29 months (range 8-123 months) after GKS. The treatment outcomes were compared with 80 case-matched controls who underwent GKS for TN not associated with VBE. RESULTS: Intraoperative MR imaging or CT scanning revealed VBE that deformed the brainstem in 50% of patients. The trigeminal nerve was displaced in cephalad or lateral planes in 60%. In 4 patients (20%), the authors could identify only the distal cisternal component of the trigeminal nerve as it entered into the Meckel cave. After GKS, 15 patients (75%) achieved initial pain relief that was adequate or better, with or without medication (Barrow Neurological Institute [BNI] pain scale, Grades I-IIIb). The median time until pain relief was 5 weeks (range 1 day-6 months). Twelve patients (60%) with initial pain relief reported recurrent pain between 3 and 43 months after GKS (median 12 months). Pain relief was maintained in 53% at 1 year, 38% at 2 years, and 10% at 5 years. Some degree of facial sensory dysfunction occurred in 10% of patients. Eventually, 14 (70%) of the 20 patients underwent an additional surgical procedure including repeat GKS, percutaneous procedure, or MVD at a median of 14 months (range 5-50 months) after the initial GKS. At the last follow-up, 15 patients (75%) had satisfactory pain control (BNI Grades I-IIIb), but 5 patients (25%) continued to have unsatisfactory pain control (BNI Grade IV or V). Compared with patients without VBE, patients with VBE were much less likely to have initial (p = 0.025) or lasting (p = 0.006) pain relief. CONCLUSIONS: Pain control rates of GKS in patients with TN associated with VBE were inferior to those of patients without VBE. Multimodality surgical or medical management strategies were required in most patients with VBE.

BACKGROUND: Trigeminal neuralgia (TN) may recur after treatment by gamma knife stereotactic radiosurgery (GKSR). OBJECTIVE: To evaluate management outcomes in patients who underwent repeat GKSR for TN. METHODS: The authors reviewed their experience with repeat GKSR in 119 patients with recurrent TN. The median patient age was 74 years (range, 34-96 years). The median interval between procedures was 26 months. The median target dose for repeat GKSR was 70 Gy (range, 50-90 Gy) and the median cumulative dose was 145 Gy (range, 120-170 Gy). The median follow-up was 48 months (range, 6-187 months) after repeat GKSR. RESULTS: After repeat GKSR, 87% of patients achieved initial pain relief (Barrow Neurological Institute pain score I-IIIb). Pain relief was maintained in 87.8% at 1 year, 69.8% at 3 years, and 44.2% at 5 years. Facial sensory dysfunction occurred in 21% of patients within 18 months after GKSR. Longer pain relief was observed in patients who had recurrent pain in a reduced pain distribution of the face compared with the pain distribution at the time of their initial GKSR, and in those who developed additional trigeminal sensory loss after a repeat procedure. A cumulative edge of brainstem dose >/= 44 Gy was more likely to be associated with the development of sensory loss. CONCLUSION: Repeat GKSR provides a similar rate of pain relief as the first procedure. The best responses were observed in patients who had good pain control after the first procedure and those who developed new sensory dysfunction in the affected trigeminal distribution.

Object Microsurgical management of foramen magnum meningiomas (FMMs) can be associated with significant morbidity and mortality. Stereotactic radiosurgery may be an efficient and safe alternative treatment modality for such tumors. The object of this study was to increase the documented experience with Gamma Knife surgery (GKS) for FMMs and to delineate its role in an overall management paradigm. Methods The authors report on their experience with 24 patients harboring FMMs managed with GKS. Twelve patients had primary symptomatic tumors, 5 had asymptomatic but enlarging primary tumors, and 7 had recurrent or residual tumors after a prior surgery. Results Follow-up clinical and imaging data were available in 21 patients at a median follow-up of 47 months (range 3-128 months). Ten patients had measurable tumor regression, which was defined as an overall volume reduction > 25%. Eleven patients had no further tumor growth. Two patients died as a result of advanced comorbidities before follow-up imaging. One patient was living 8 years after GKS but had no clinical evaluation. Ten of 17 symptomatic patients with at least 6 months of follow-up had symptom improvement, and 7 remained clinically stable. Smaller tumors were more likely to regress. No patient suffered an adverse radiation effect after radiosurgery. Conclusions Gamma Knife surgery was a safe management strategy for small, minimally symptomatic, or growing FMMs as well as for residual tumors following conservative microsurgical removal.

PURPOSE: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. METHODS AND MATERIALS: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up >/=6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. RESULTS: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age 70 years, and partly atypical Type 2 trigeminal neuralgia, respectively. CONCLUSIONS: The use of carbamazepine or gabapentin at the time of radiosurgery does not decrease the rates of obtaining partial or complete pain relief after radiosurgery, but gabapentin may reduce the risks of developing post-radiosurgery trigeminal neuropathy.

To assess outcomes after stereotactic radiosurgery (SRS) for chondrosarcomas of the skull base, we reviewed 22 patients with cranial base chondrosarcomas who underwent SRS between 1987 and 2009. The median patient age was 42 years (range, 15-75). The median SRS target volume was 8.0 cc (range, 0.9-28.2) and median margin dose was 15.0 Gy (range, 10.5-20). 15 patients (68 %) underwent one or more tumor resections and 3 of these patients also had fractionated radiation therapy. At a median follow-up of 75 months after SRS, seven patients died due to tumor progression. The actuarial overall survival after SRS for the entire group of chondrosarcoma patients was 95, 76, 70 and 56 % at 1, 3, 5 and 10 years, respectively. Factors associated with longer survival after SRS included patient age >40 years, a shorter interval (<6 months) between diagnosis and SRS, and either no or a single prior resection. Treated tumor control rates were 91, 72, 72 and 54 % at 1, 3, 5 and 10 years, respectively. Factors associated with longer progression-free survival after SRS included patient age >40 years and no prior RT. Symptomatic adverse radiation effects occurred in two patients (10 %). Stereotactic radiosurgery may provide a benefit to patients as either a primary or adjuvant therapy. The ability to achieve tumor control in patients with chondrosarcoma is likely to be enhanced by earlier timing of SRS after diagnosis and multimodal management, beginning with resection when feasible followed by early SRS for progressive residual tumor.